Carbon monoxide poisoning.

Carbon monoxide (CO) is a toxic gas that is invisible, odorless, colorless, non-irritating, and tasteless. CO is a by-product of incomplete combustion of carbon-containing materials. With CO being as old as fire itself, one can only imagine the number of cases of CO poisoning that would have been seen in the emergency department at "Homo Erectus Community Hospital" had it existed 700 to 800 thousand years ago when the cave dwelling Peking Man began using fire for cooking and cave warming!

Ironically, CO is manufactured in the body as a result of the breakdown of hemoglobin. Consequently, normal people may have a COHb concentration of 0.5% in their blood. Smokers often have COHb levels of 10% or higher.

Historical Background

Not until coal was used as a domestic fuel did CO poisoning become a recognized medical problem. Homes and industry relied on gas from coal and oil for heating and lighting. Edgar Allen Poe (1809-1849) unwittingly wrote about his symptoms of CO poisoning from gas lighting in many of his short stories. In his fittingly titled story, "Loss of Breath," Poe wrote, "The sensations of my illness were much like those of a man upon the gallows: I heard my heart beating with violence--the veins in my hands and wrists were swelling to nearly bursting--my temple throbbed tempestuously--and I felt my eyes were starting from my sockets ... Confusion crowded upon confusion like a wave upon a wave." Poe related numerous other symptoms in his writings. After Poe's death on October 7, 1849, the Baltimore health commissioner listed the cause of death as "congestion of the brain."

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In 1857, in France, a French physiologist named Claude Bernard carried out an animal experiment and noticed how the animal's venous blood was as cherry red as blood in arterial circulation. Still puzzled as to what CO did to kill the animal, Bernard took a sample of arterial blood from a healthy animal, placed this blood beneath a layer of liquid mercury in a test tube containing CO gas. Maintaining an air-tight seal, Bernard shook the tube to achieve contact between the blood and the CO. He then analyzed the gas in the test tube and found it was oxygen-enriched. Bernard concluded that the CO displaced the O2 in the blood and that the CO "remained fixed in the blood corpuscles," causing the demise of the animal.

Epidemiology

CO is the leading cause of morbidity and mortality by poisoning in the United States. Because many cases of CO poisoning go undetected and unreported, the actual incidence of this poisoning is unknown. Estimates are that approximately one-third of all cases are undiagnosed because CO poisoning mimics a variety of systemic diseases.

Common sources of CO are wood and gas burning fireplaces, internal combustion engine exhausts, gas and oil furnaces, space heaters, coal and wood stoves, electric ovens in the self-cleaning mode, and tobacco smoking.

Pathophysiology

CO severely interferes with tissue oxygenation. Both O2 and CO bind reversibly with hemoglobin. These two gases compete for binding with the four hemes in the hemoglobin molecule. However, the magnitude of hemoglobin's affinity for CO is 210 to 240 times greater than for O2. Additionally, the binding of CO to hemoglobin to form carboxyhemoglobin (HbCO) causes conformational changes to hemoglobin's tetrameric structure, thereby increasing the affinity of the remaining heme groups for O2. In other words, when a CO molecule binds with one of the four hemes on a hemoglobin molecule, the other three hemes cling to O2 more avidly. The result is a leftward shift of the oxyhemoglobin dissociation curve, and a compromised tissue O2 delivery. The greater affinity of hemoglobin for CO accounts for the fact that only a small amount of inspired CO causes a large COHb level in the blood. For example, inhalation of 0.1% CO produces a COHb level of 10%.

Myoglobin is another heme-containing molecule that binds avidly with CO. Skeletal and cardiac muscle are adversely affected by this binding. Carboxymyoglobin poses a serious threat to a CO victim because the myocardium can be severely deprived of oxygenation. The associated cardiac ischemia can cause lethal dysrythmias. The binding of CO to cardiac myoglobin also has a depressant effect on the heart, producing hypotension. Both of these effects exacerbate the decreased tissue O2 delivery. Interestingly, CO dissociates from myoglobin much more slowly than CO does from hemoglobin. Consequently, as CO leaves myoglobin, CO re-enters the blood where the COHb level rises again. Outside the vasculature CO binds with cytochrome A3, an enzyme involved in the electron transport chain within the process of oxidative phosphorylation. Oxidative phosphorylation involves the production of ATP from ADP and phosphate by harnessing the energy released as electrons are transferred during a series of oxidation-reduction reactions at the cellular level. Therefore, CO poisoning interferes with cellular respiration, i.e., the body's ability to produce energy.

CO also interferes with cytochrome P450 in the liver. Cytochrome P450 is a group of enzymes involved in the body's detoxification process. The ability of CO to inhibit the cytochrome system accounts for the profound neurological depression that often continues beyond the time COHb levels have been reduced to below toxic concentrations.

Brain lipid peroxidation and leukocyte-mediated inflammatory alterations also occur during CO poisoning. A chain of biochemical reactions is triggered by the presence of CO in the brain leading to the formation of the oxygen metabolite, superoxide anion. This oxygen radical causes lipid peroxidation and ultimately brain damage. This mechanism is similar to ischemia-reperfusion injury associated with hypoperfusion.

Clinical Manifestations

The clinical manifestations of CO poisoning are neurological and cardiovascular because the brain and heart are most vulnerable to the lethal properties of CO. Common symptoms include: headache, fatigue, muscle pain and cramps, nausea, vomiting, diarrhea, confusion, memory loss, dizziness, chest pain, rapid heartbeat, shortness of breath, and hearing and visual impairment. Although the signs and symptoms of acute CO poisoning are variable, textbooks often cite a positive correlation between COHb levels and clinical manifestations. For example,

COHb%  Clinical Manifestations

10%    asymptommatic or headaches
20%    dizziness, nausea, syncope
30%    visual disturbances
40%    confusion & syncope
50%    seizures & coma
60%    cardiopulmonary dysfunction/death

Difficulty only occurs when attempting to correlate COHb% and clinical manifestations, and when trying to predict sequelae.

Diagnosis

The PaO2 will remain normal because CO inhalation affects O2 attached to hemoglobin, and not O2 dissolved in the plasma. An SaO2 value obtained from the analysis of an arterial blood sample is meaningless because the SaO2 is calculated rather than measured. A pulse oximeter will render a falsely high SpO2 in the presence of COHb. Therefore, for accuracy, the level of COHb in the blood must be measured by a cooximeter.

Physicians must remain vigilant for CO poisoning signs and symptoms especially during the winter months when risk from CO exposure is high. Because flu symptoms mimic those of CO poisoning, whenever two or more persons enter the emergency department exhibiting flu-like symptoms, CO exposure should be suspected. A CO analyzer can be used to measure a victim's exhaled CO concentration.

Treatment

Anyone suspected of experiencing CO poisoning should receive 100% O2. The purpose is to improve the competition of O2 for hemoglobin binding sites. The half-life of CO in a victim's blood is about 5 hours when room air is breathed, compared to one hour when the FIO2 is 1.0. The half-life is further reduced to about 20 minutes when hyperbaric O2 therapy (HBOT) is administered at 100% O2 at 3 atmospheres. Most CO victims can be treated under normobaric conditions. HBOT should be reserved for patients who initially fail to meet the criteria for HBOT, but experience unrelenting neurological symptoms despite hours of 100% O2 therapy. HBOT supersaturates the plasma with O2.

Research has demonstrated that HBOT inhibits the adhesion of polymorphonuclear leukocytes to the vasculature in the brain and revives inactivated cytochromes.

Prognosis

Neurological deficits occur in many patients who survive acute CO poisoning. These deficits include impaired memory, personality alterations, psychiatric impairment, visual impairment, and persistent vegetative state.

Prevention

The public should be educated concerning the sources of CO, and the operation and maintenance of certain equipment, e.g., generators and self-cleaning ovens, to prevent CO from entering the air. More home and businesses need to be equipped with CO detectors. The public should also be taught the signs and symptoms of CO exposure to recognize this condition in themselves and others.

by Bill Wojciechowski, MS, RRT